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https://www.readbyqxmd.com/read/29150335/camptothecin-psammaplin-a-hybrids-as-topoisomerase-i-and-hdac-dual-action-inhibitors
#1
Raffaella Cincinelli, Loana Musso, Roberto Artali, Mario Guglielmi, Erminia Bianchino, Francesco Cardile, Fabiana Colelli, Claudio Pisano, Sabrina Dallavalle
Recent studies have demonstrated enhanced anticancer effects of combination therapy consisting of camptothecin derivatives and HDAC inhibitors. To exploit this synergy in a single active compound, we designed new dual-acting multivalent molecules simultaneously targeting topoisomerase I and HDAC. In particular, a selected compound containing a camptothecin and the psammaplin A scaffold showed a broad spectrum of antiproliferative activity, with IC50 values in the nanomolar range. Preliminary in vivo results indicated a strong antitumor activity on human mesothelioma primary cell line MM473 orthotopically xenografted in CD-1 nude mice and very high tolerability...
November 8, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29147611/chloroquine-supplementation-increases-the-cytotoxic-effect-of-curcumin-against-her2-neu-overexpressing-breast-cancer-cells-in-vitro-and-in-vivo-in-nude-mice-while-counteracts-it-in-immune-competent-mice
#2
L Masuelli, M Granato, M Benvenuto, R Mattera, R Bernardini, M Mattei, G d'Amati, G D'Orazi, A Faggioni, R Bei, M Cirone
Autophagy is usually a pro-survival mechanism in cancer cells, especially in the course of chemotherapy, thus autophagy inhibition may enhance the chemotherapy-mediated anti-cancer effect. However, since autophagy is strongly involved in the immunogenicity of cell death by promoting ATP release, its inhibition may reduce the immune response against tumors, negatively influencing the overall outcome of chemotherapy. In this study, we evaluated the in vitro and in vivo anti-cancer effect of curcumin (CUR) against Her2/neu overexpressing breast cancer cells (TUBO) in the presence or in the absence of the autophagy inhibitor chloroquine (CQ)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147526/a-ratiometric-fluorescent-probe-for-imaging-and-quantifying-anti-apoptotic-effects-of-gsh-under-temperature-stress
#3
Xiaoyue Han, Xinyu Song, Fabiao Yu, Lingxin Chen
Hypothermia and hyperthermia are cell stressed states resulting from environmental temperature changes, which can abnormally decrease intracellular glutathione (GSH) concentrations and induce apoptosis. As the most abundant intracellular non-protein biothiol, GSH can protect cells from apoptosis. Considering the important roles of GSH in the anti-apoptotic process in cells and in vivo, we strive to develop a powerful chemical tool for the direct detection of GSH concentration changes under temperature stress...
October 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29146731/organic-anion-transporting-polypeptide-1b3-as-a-dual-reporter-gene-for-fluorescence-and-magnetic-resonance-imaging
#4
Menq-Rong Wu, Hon-Man Liu, Chen-Wen Lu, Way-Hone Shen, I-Jou Lin, Li-Wen Liao, Yi-You Huang, Ming-Jium Shieh, Jong-Kai Hsiao
Reporter proteins have broad applications in visualizing molecular events at the cellular, tissue and whole-body levels. Transmembrane transporters recognizing specific molecular domains are of particular interest because they enable the migration of signal-source molecules from the extracellular space to the cytoplasm for subsequent application in multimodality imaging. Organic anion-transporting polypeptides (OATPs) have demonstrated their MRI reporter efficacy. We further expanded their use as a dual-modality reporter in MRI and noninvasive in vivo imaging system (IVIS)...
November 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29146721/development-of-a-function-blocking-antibody-against-fibulin-3-as-targeted-reagent-for-glioblastoma
#5
Mohan Sobhana Nandhu, Prajna Behera, Vivek Bhaskaran, Sharon L Longo, Lina M Barrera-Arenas, Sadhak Sengupta, Diego J Rodriguez-Gil, E Antonio Chiocca, Mariano S Viapiano
PURPOSE: We sought a novel approach against glioblastomas (GBM) focused on targeting signaling molecules localized in the tumor extracellular matrix (ECM). We investigated fibulin-3, a glycoprotein that forms the ECM scaffold of GBMs and promotes tumor progression by driving Notch and NF-kB signaling. EXPERIMENTAL DESIGN: We used deletion constructs to identify a key signaling motif of fibulin-3. A monoclonal antibody (mAb428.2) was generated against this epitope and extensively validated for specific detection of human fibulin-3...
November 16, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29146698/characterization-of-site-specifically-conjugated-monomethyl-auristatin-e-and-duocarmycin-based-anti-psma-antibody-drug-conjugates-for-treatment-of-psma-expressing-tumors
#6
Susanne Lütje, Danny Gerrits, Janneke D Molkenboer-Kuenen, Ken Herrmann, Giulio Fracasso, Marco Colombatti, Otto C Boerman, Sandra Heskamp
Rationale: Prostate cancer (PCa) is the most common cancer in men worldwide. In general, PCa responds poorly to chemotherapy. Therefore, antibody-drug conjugates (ADCs) have been developed to specifically deliver highly cytotoxic drugs to the tumor. As the prostate-specific membrane antigen (PSMA) is overexpressed in PCa, it represents a promising target for ADC-based therapies. The aim of this study was to evaluate the therapeutic efficacy of site-specifically conjugated duocarmycin- and monomethyl auristatin E (MMAE)-based anti-PSMA ADCs with drug-antibody ratios (DARs) of 2 and 4...
November 16, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29146630/a-role-for-cxcr4-in-peritoneal-and-hematogenous-ovarian-cancer-dissemination
#7
Agnes Figueras, Elisenda Alsina-Sanchís, Alvaro Lahiguera, Manuel Abreu, Laura Muinelo-Romay, Gema Moreno-Bueno, Oriol Casanovas, Mariona Graupera, Xavier Matias-Guiu, August Vidal, Alberto Villanueva, Francesc Viñals
Epithelial ovarian cancer is characterized by a low recovery rate because the disease is typically diagnosed at an advanced stage, by which time, most patients (80%) already exhibit disseminated neoplasia. The cytokine receptor CXCR4 has been implicated in the development of metastasis in various tumor types. Using a patient-derived tissue macroarray and mRNA expression analysis we observed high CXCR4 levels in high-grade serous epithelial ovarian carcinomas, the most metastatic tumor, compared with those in endometrioid carcinomas...
November 16, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29143983/growth-of-doxorubicin-resistant-undifferentiated-spindle-cell-sarcoma-pdox-is-arrested-by-metabolic-targeting-with-recombinant-methioninase
#8
Kentaro Igarashi, Shukuan Li, Qinghong Han, Yuying Tan, Kei Kawaguchi, Takashi Murakami, Tasuku Kiyuna, Kentaro Miyake, Yunfeng Li, Scott D Nelson, Sarah M Dry, Arun S Singh, Irmina A Elliott, Tara A Russell, Mark A Eckardt, Norio Yamamoto, Katsuhiro Hayashi, Hiroaki Kimura, Shinji Miwa, Hiroyuki Tsuchiya, Fritz C Eilber, Robert M Hoffman
Undifferentiated spindle-cell sarcoma (USCS) is a recalcitrant -cancer in need of individualized therapy. A high-grade USCS from a striated muscle of a patient was grown orthotopically in the right biceps femoris muscle of nude mice to establish a patient-derived orthotopic xenograft (PDOX) model. In a previous study, we evaluated the efficacy of standard first-line chemotherapy of doxorubicin (DOX), gemcitabine (GEM) combined with docetaxel (DOC), compared to pazopanib (PAZ), a multi-targeting tyrosine-kinase inhibitor, in an USCS PDOX model...
November 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29143449/osteoinductivity-of-nanostructured-hydroxyapatite-functionalized-gelatin-modulated-by-human-and-endogenous-mesenchymal-stromal-cells
#9
E Della Bella, A Parrilli, A Bigi, S Panzavolta, S Amadori, G Giavaresi, L Martini, V Borsari, M Fini
The demand of new strategies for the induction of bone regeneration is continuously increasing. Biomimetic porous gelatin-nanocrystalline hydroxyapatite scaffolds with tailored properties were previously developed, showing a positive response in terms of cell adhesion, proliferation, and differentiation. In the present paper, we focused on their osteoinductive properties. The effect of scaffolds on osteogenic differentiation of human mesenchymal stromal cells (hMSCs) was investigated in vitro. hMSCs were seeded on GEL (type A gelatin) and GEL containing 10wt% hydroxyapatite (GEL-HA) and cultured in osteogenic medium...
November 16, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/29143362/microrna-26a-inhibits-proliferation-and-tumorigenesis-via-targeting-cks2-in-laryngeal-squamous-cell-carcinoma
#10
Zhiyan Wu, Baocai Lu, Xiao Li, Wenjie Miao, Jin Li, Yongjuan Shi, Wenfa Yu
Laryngeal squamous cell carcinoma (LSCC) is one of the most common head and neck cancer, with high mortality and incidence. MicroRNA-26a (miR-26a) is involved in the development and progression of several tumors. However, the roles of miR-26a and its target CKS2 in LSCC progression are not yet clear. The mRNA and protein expression was determined using RT-PCR and Western blotting assay, respectively. Cell proliferation was detected using a Cell Counting kit-8 assay (CCK-8). Transwell assay was used to evaluate cell migration and invasion...
November 16, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29140069/dual-functions-of-cyclometalated-iridium-iii-complexes-anti-metastasis-and-lysosome-damaged-photodynamic-therapy
#11
Fang-Xin Wang, Mu-He Chen, Yan-Nan Lin, Hang Zhang, Cai-Ping Tan, Liang-Nian Ji, Zongwan Mao
Four phosphorescent cyclometalated iridium(III) complexes containing benzimidazole moiety have been designed and synthesized. These Ir(III) complexes can inhibit several cancerous processes including cell migration, invasion, colony formation and angiogenesis effectively. Interestingly, they show much higher singlet oxygen quantum yield in acidic solution than in neutral solution. Upon irradiation at 425 nm with low energy (1.2 J·cm(-2)), they can induce apoptosis through lysosomal damage, evaluation of ROS level and activation of caspase-3/7...
November 15, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29139602/cell-yield-chondrogenic-potential-and-regenerated-cartilage-type-of-chondrocytes-derived-from-ear-nasoseptal-and-costal-cartilage
#12
Aijuan He, Huitang Xia, Kaiyan Xiao, Tingting Wang, Yu Liu, Jixin Xue, Dan Li, Shengjian Tang, Fangjun Liu, Xiaoyun Wang, Wenjie Zhang, Wei Liu, Yilin Cao, Guangdong Zhou
Functional reconstruction of large cartilage defects in subcutaneous sites remains clinically challenging because of limited donor cartilage. Tissue engineering is a promising and widely accepted strategy for cartilage regeneration. To date however, this strategy has not achieved a significant breakthrough in clinical translation owing to a lack of detailed pre-clinical data on cell yield and functionality of clinically applicable chondrocytes. To address this issue, the current study investigated the initial cell yield, proliferative potential, chondrogenic capacity, and regenerated cartilage-type of human chondrocytes derived from auricular (AU), nasoseptal (NS), and costal (CO) cartilage using a scaffold-free cartilage regeneration model (cartilage sheet)...
November 15, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/29139598/preparation-and-comparative-evaluation-of-99m-tc-hynic-cngr-and-99m-tc-hynic-peg2-cngr-as-tumor-targeting-molecular-imaging-probes
#13
Kusum Vats, Drishty Satpati, Rohit Sharma, Chandan Kumar, Haladhar Dev Sarma, Sharmila Banerjee
The tripeptide sequence NGR (asparagine-glycine-arginine) specifically recognizes aminopeptidase N (APN or CD13) receptors highly expressed on tumor cells as well as tumor vasculature. Thus NGR peptides can precisely deliver therapeutic and diagnostic compounds to CD13 expressing cancer sites. In this regard two NGR peptide ligands, HYNIC-c(NGR) and HYNIC-PEG2 -c(NGR) were synthesized, radiolabeled with (99m) Tc and evaluated in CD13-positive human fibrosarcoma HT-1080 tumor xenografts. The radiotracers, (99m) Tc-HYNIC-c(NGR) and (99m) Tc-HYNIC-PEG2 -c(NGR) could be prepared in ~95% radiochemical purity (RCP) and exhibited excellent in vitro and in vivo stability...
November 15, 2017: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/29138558/%C3%AE-v%C3%AE-3-integrin-targeted-micellar-mertansine-prodrug-effectively-inhibits-triple-negative-breast-cancer-in-vivo
#14
Ping Zhong, Xiaolei Gu, Ru Cheng, Chao Deng, Fenghua Meng, Zhiyuan Zhong
Antibody-mertansine (DM1) conjugates (AMCs) are among the very few active targeting therapeutics that are approved or clinically investigated for treating various cancers including metastatic breast cancer. However, none of the AMCs are effective for the treatment of triple-negative breast cancers (TNBCs). Here, we show that cRGD-decorated, redox-activatable micellar mertansine prodrug (cRGD-MMP) can effectively target and deliver DM1 to αvβ3 integrin overexpressing MDA-MB-231 TNBC xenografts in nude mice, resulting in potent tumor growth inhibition...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29138118/8-cetylberberine-inhibits-growth-of-lung-cancer-in-vitro-and-in-vivo
#15
Yubo Xiao, Cheng Tian, Tao Huang, Bing Han, Meimei Wang, Hang Ma, Zhaoxing Li, Xiaoli Ye, Xuegang Li
AIMS: This study is aimed at detecting the anti-tumor efficacy of a new berberine (BBR) derivative 8-cetylberberine (HBBR), which has a significant improvement in hydrophobicity and pharmacological effects compared to BBR. MAIN METHODS: The human non-small lung cancer cell line A549 and normal human lung epithelial cells (MRC-5) were cultured to observe inhibition in vitro. Cell viability was analyzed via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay...
November 11, 2017: Life Sciences
https://www.readbyqxmd.com/read/29137437/dna-hypermethyation-and-silencing-of-pitx1-correlated-with-advanced-stage-and-poor-postoperative-prognosis-of-esophageal-squamous-cell-carcinoma
#16
Takeshi Otsubo, Kazuhiko Yamada, Teruki Hagiwara, Kenshiro Oshima, Kei Iida, Koro Nishikata, Tetsuro Toyoda, Toru Igari, Kyoko Nohara, Satoshi Yamashita, Masahira Hattori, Taeko Dohi, Yuki I Kawamura
Esophageal squamous cell carcinoma (ESCC) is associated with the accumulation of genetic and epigenetic changes in the background mucosa. Dysregulated DNA methylation is known to lead to the inactivation of tumor suppressor genes and the activation of oncogenes. To identify the genes whose expression is perturbed by abnormal DNA methylation in ESCC, integrative transcriptomics by serial analysis of gene expression (SAGE) and methylome sequencing by methyl-DNA immunoprecipitation (MeDIP) analysis were performed...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137407/lncrna-snhg12-contributes-to-multidrug-resistance-through-activating-the-mapk-slug-pathway-by-sponging-mir-181a-in-non-small-cell-lung-cancer
#17
Pei Wang, Dong Chen, Hongbing Ma, Yong Li
Small nucleolar RNA host gene 12 (SNHG12), as one of the long non-coding RNAs (lncRNAs), plays an oncogenic role in various cancers, however, its role in the chemoresistance of non-small cell lung cancer (NSCLC) is unclear. In this study, we investigated the effect of SNHG12 on multidrug resistance (MDR) in NSCLC. The results showed that SNHG12 was high-expressed and miR-181a was low-expressed in NSCLC tumor tissues and cell lines. Knockdown of SNHG12 reversed the resistance to cisplatin, paclitaxel and gefitinib in A549/DDP, A549/PTX and PC9/AB2 cells through inducing cell apoptosis...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137372/microrna-33a-5p-increases-radiosensitivity-by-inhibiting-glycolysis-in-melanoma
#18
Ke Cao, Jingjing Li, Jia Chen, Li Qian, Aijun Wang, Xiang Chen, Wei Xiong, Jintian Tang, Shijie Tang, Yong Chen, Yao Chen, Yan Cheng, Jianda Zhou
Glycolysis was reported to have a positive correlation with radioresistance. Our previous study found that the miR-33a functioned as a tumor suppressor in malignant melanoma by targeting hypoxia-inducible factor1-alpha (HIF-1α), a gene known to promote glycolysis. However, the role of miR-33a-5p in radiosensitivity remains to be elucidated. We found that miR-33a-5p was downregulated in melanoma tissues and cells. Cell proliferation was downregulated after overexpression of miR-33a-5p in WM451 cells, accompanied by a decreased level of glycolysis...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137357/akr7a3-suppresses-tumorigenicity-and-chemoresistance-in-hepatocellular-carcinoma-through-attenuation-of-erk-c-jun-and-nf-%C3%AE%C2%BAb-signaling-pathways
#19
Raymond Kwok Kei Chow, Sarah Tsz-Kwan Sin, Ming Liu, Yan Li, Tim Hon Man Chan, Yangyang Song, Leilei Chen, Dora Lai-Wan Kwong, Xin-Yuan Guan
Hepatocellular carcinoma (HCC), which accounts for 85-90% of primary liver cancer, is now the second leading cause of cancer-related mortality worldwide. Here we reported that Aldo-Keto Reductase family 7A isoform 3 (AKR7A3) is frequently down-regulated in HCC, associating with poor overall survival rate, elevated serum α-fetoprotein (AFP) and poor differentiation of HCC. The promoter region of AKR7A3 was detected to be hypermethylated. Loss of heterozygosity (LOH) was also detected in AKR7A3. Functional assays on both AKR7A3 overexpressed and knockdown cells, including foci formation, colony formation in soft agar, migration, invasion and tumor formation in nude mice, demonstrated the strong tumor suppressive functions of AKR7A3...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137354/erps294-is-a-biomarker-of-ligand-or-mutational-er%C3%AE-activation-and-a-breast-cancer-target-for-cdk2-inhibition
#20
Gary K Scott, David Chu, Ravneet Kaur, Julia Malato, Daniel E Rothschild, Katya Frazier, Serenella Eppenberger-Castori, Byron Hann, Ben Ho Park, Christopher C Benz
ERα phosphorylation at hinge site S294 (pS294) was recently shown to be essential for ER-dependent gene transcription and mediated by an unknown cyclin-dependent kinase (CDK). This study was undertaken to identify the exact CDK pathway mediating pS294 formation, and to determine if this phosphorylation event occurs with, and can be targeted to treat, the ligand-independent growth of breast cancers expressing endocrine-refractory ESR1 mutations. Using a newly developed anti-pS294 monoclonal antibody, a combination of CDK specific siRNA knockdown studies and a broad panel of CDK selective inhibitors against ligand (E2)-stimulated MCF7 cells, we first identified CDK2 as the primary mediator of pS294 formation and showed that CDK2-selective inhibitors like Dinaciclib, but not CDK4/6 inhibitors like Palbociclib, can selectively prevent pS294 formation and repress ER-dependent gene expression...
October 13, 2017: Oncotarget
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